Literature DB >> 22890269

Oxidative stress and caspase-mediated fragmentation of cytoplasmic domain of erythrocyte band 3 during blood storage.

Sara Rinalducci1, Emanuela Ferru, Barbara Blasi, Francesco Turrini, Lello Zolla.   

Abstract

BACKGROUND: During blood bank storage, red blood cells (RBCs) undergo a number of biological and biochemical alterations collectively referred to as "storage lesions". These injuries include loss and oxidative cross-linking of band 3, the major integral protein of RBC membranes. Denaturation of hemoglobin (Hb) and damage to the amino-terminal of band 3 are recognised as the starting events for immunological recognition mechanisms and phagocytic removal of senescent or impaired RBCs from circulation. Consequently, studies focusing on the Hb-association and oxidative status of the cytoskeleton of stored RBCs intended for transfusion are of extreme interest. In this work, two storage-related fragments of band 3 were documented and biochemically characterised.
METHODS: Four RBC units were collected from normal volunteers and stored for 21 days under (i) standard blood bank conditions, (ii) anaerobic conditions, or (iii) in the presence of caspase 3-inhibitor. Degradation products of band 3 were followed by sodium dodecyl sulfatepolyacrylamide gel electrophoresis coupled with western blot and mass spectrometry analyses.
RESULTS: Two different degradation products of the cytoplasmic domain of the erythrocyte band 3 (CDB3) were detected in RBC membranes during storage in saline-adenine-glucosemannitol (SAGM) preservation medium. One of these fragments showed an apparent molecular weight of 34 kDa and was demonstrated to be the product of a free-radical attack on the protein main chain, whereas another fragment of 24 kDa was the result of a caspase 3-mediated cleavage. DISCUSSION: Although to different extent, anaerobic conditions reduced the formation of both truncated products indicating an enhanced activity of the pro-apoptotic caspase 3 enzyme following oxidative stress. Interestingly, both CDB3 fragments were tightly associated to the erythrocyte membrane supporting the involvement of Cys-201 and/or Cys-317 in clustering different band 3 monomers.

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Year:  2012        PMID: 22890269      PMCID: PMC3418627          DOI: 10.2450/2012.009S

Source DB:  PubMed          Journal:  Blood Transfus        ISSN: 1723-2007            Impact factor:   3.443


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5.  Characterization of the reversible conformational equilibrium of the cytoplasmic domain of erythrocyte membrane band 3.

Authors:  P S Low; M A Westfall; D P Allen; K C Appell
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